Lometrexol disodium  (Synonyms: DDATHF disodium)

Lometrexol (DDATHF) disodium, an antipurine antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol disodium can further inhibit de novo purine synthesis, causing abnormal cell proliferation and apoptosis, even cell cycle arrest. Lometrexol disodium has anticancer activity. Lometrexol disodium also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor^[1][2][3].

Lometrexol (DDATHF) disodium binds tightly to GART, resulting in a rapid and prolonged depletion of intracellular purine ribonucleotides^[3].
Lometrexol (1-30 μM; 2-10 hours) disodium induces rapid and complete growth inhibition in L1210 cells^[3].
Lometrexol (1 μM; 2-24 hours) disodium induces cell cycle arrest in murine leukemia L1210 cells^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Lometrexol (DDATHF; i.p.; 15-60 mg/kg; on gestation day 7.5) disodium induces neural tube defects (NTDs) by disturbing purine metabolism and increases the rate of embryonic resorption and growth retardation in a dose-dependent manner^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) disodium decreases glycinamide ribonucleotide formyl transferase (GARFT) activity and Changes of ATP, GTP, dATP and dGTP levels^[1].
Lometrexol (i.p.; 40 mg/kg; on gestation day 7.5) disodium induces abnormal proliferation and apoptosis exist in neural tube defects (NTDs)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

487.42

C₂₁H₂₃N₅Na₂O₆

120408-07-3

固体

White to light yellow

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Xu L, et, al. The effect of inhibiting glycinamide ribonucleotide formyl transferase on the development of neural tube in mice. Nutr Metab (Lond). 2016 Aug 23;13(1):56.  [Content Brief]

  [2]. Scaletti E, et, al. Structural basis of inhibition of the human serine hydroxymethyltransferase SHMT2 by antifolate drugs. FEBS Lett. 2019 Jul;593(14):1863-1873.  [Content Brief]

  [3]. Bronder JL, et, al. Antifolates targeting purine synthesis allow entry of tumor cells into S phase regardless of p53 function. Cancer Res. 2002 Sep 15;62(18):5236-41.  [Content Brief]